Archive for the ‘3D Plotting Scaffolds’ Category

New method for 3D imaging of brain tumors

Posted in 3D Plotting Scaffolds, Biomedical Measurement Science, Cancer and Current Therapeutics, MicroEngineering Cell-Tissue & Systems, Neurological Diseases, tagged 3D surgical guides, glioblasoma on May 1, 2016| Leave a Comment »

New method for 3D imaging of brain tumors

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

 

Third-Harmonic Generation Microscopy Provides In Situ Brain Tumor Imaging

AMSTERDAM, Netherlands, April 25, 2015 — A technique involving third-harmonic generation microscopy could allow neurosurgeons to image and assess brain tumor boundaries during surgery, providing optical biopsies in near-real time and increasing the accuracy of tissue removal.

Pathologists typically use staining methods, in which chemicals like hematoxylin and eosin turn different tissue components blue and red, revealing its structure and whether there are any tumor cells. A definitive diagnosis can take up to 24 hours, meaning surgeons may not realize some cancerous tissue has escaped from their attention until after surgery — requiring a second operation and more risk.

Tissue from a patient diagnosed with low-grade glioma. The green image is taken with the new method, while the pink uses conventional hematoxylin and eosin staining. From the upper left to the lower right, both images show increasing cell density due to more tumor tissue. The insets reveal the high density of tumor cells. Courtesy of N.V. Kuzmin et al./VU University Amsterdam.

Brain tumors — specifically glial brain tumors — are often spread out and mixed in with the healthy tissue, presenting a particular challenge. Surgery, irradiation and chemotherapy often cause substantial collateral damage to the surrounding brain tissue.

Now researchers from VU University Amsterdam, led by professor Marloes Groot, have demonstrated a label-free optical method for imaging cancerous brain tissue. They were able to produce most images in under a minute; smaller ones took <1 s, while larger images of a few square millimeters took 5 min.

The study involved firing short, 200-fs, 1200-nm laser pulses into the tissue. When three photons converged at the same time and place, the photons interacted with the nonlinear optical properties of the tissue. Through the phenomena of third harmonic generation, the interactions produced a single 400- or 600-nm photon (in the case of third or second harmonic generation, respectively).

The shorter-wavelength photon scatters in the tissue, and when it reaches a detector — in this case a high-sensitivity GaAsP photomultiplier tube — it reveals what the tissue looks like inside. The resulting images enabled clear recognition of cellularity, nuclear pleomorphism and rarefaction of neuropil in the tissue.

While this technique has been used in other applications — to image insects and fish embryos, for example — the researchers said this is the first time it’s been used to analyze glial brain tumors.

Groot and her team are now developing a handheld device for tumor border detection during surgery. The incoming laser pulses can only reach a depth of about 100 μm into the tissue currently; to reach further, Groot envisions attaching a needle that can pierce the tissue and deliver photons deeper.

The research was published in Biomedical Optics Express, a publication of The Optical Society (OSA) (doi: 10.1364/boe.7.001889).

 

Third harmonic generation imaging for fast, label-free pathology of human brain tumors

N. V. Kuzmin, P. Wesseling, P. C. de Witt Hamer, D. P. Noske, G. D. Galgano, H. D. Mansvelder, J. C. Baayen, and M. L. Groot

Biomedical Optics Express 2016  7(5):1889-1904    doi: 10.1364/BOE.7.001889

In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies.

 

Glial tumors (gliomas) account for almost 80% of the tumors originating from brain tissue. The vast majority of these tumors are so-called ‘diffuse gliomas’ as they show very extensive (‘diffuse’) growth into the surrounding brain parenchyma. With surgical resection, irradiation, and/or chemotherapy it is impossible to eliminate all glioma cells without serious damage to the brain tissue. As a consequence, until now, patients with a diffuse glioma have had a poor prognosis, a situation which strongly contributes to the fact that brain tumor patients experience more years of life lost than patients with any other type of cancer [1,2].

Meanwhile it has also been demonstrated that the prognosis of patients with a diffuse glioma correlates with the extent of resection [3–5]. During brain surgery, however, it is extremely difficult for the neurosurgeon to determine the boundary of the tumor, i.e. whether a brain area contains tumor cells or not. If the neurosurgeon could have histopathological information on the tumor boundaries during brain surgery, then recognition of these tumor boundaries and with that, the surgical resection, could be significantly improved.

Occasionally, intra-operative analysis using hematoxylin-and-eosin (H&E) stained sections of snap-frozen material or smear preparations is performed by the pathologist to help establish brain tumor boundaries, but this procedure only allows analysis of small, selected regions, can only be performed on tissue fragments that are already resected, and is rather time consuming (frozen section diagnosis) or does not allow analysis of tumor in the histological context (smear preparations). Fluorescence imaging techniques are increasingly used during surgery [6,7] but are associated with several drawbacks, such as heterogeneous delivery and nonspecific staining [8,9]. In particular, low-grade gliomas and normal brain tissue have an intact blood-brain barrier and take up little circulating dye [10–12]. Alternative techniques are therefore required, that can detect the presence of tumor cells in tissue without fluorescent labels and with a speed that enables ‘live’ feedback to the surgeon while he/she operates.

The past year has seen exciting new developments in which optical coherence tomography [13] and stimulated Raman microscopy [14,15] were reported to reliably detect tumor tissue in the brain of human glioma patients, and a handheld Raman spectroscopy device was even implemented intra-surgical to assess brain tissue prior to excision [16]. These techniques are especially sensitive in densely tumor-infiltrated areas, and for the Raman spectroscopy device study a sensitivity limit of 17 tumor cells in an area of 150 × 150 μm² was reported. The discriminating power of the Raman techniques is based on subtle differences in the vibrational spectra of tumor tissue and healthy tissue, and they require extensive comparison of experimental spectra against libraries of reference spectra. A technique capable of directly visualizing the classical histopathological hallmark criteria currently used by pathologists for classification of tumor tissue could potentially be even more reliable and make the transition from the current practice—histopathological analysis of fixated tissue—to in situ optical biopsy easier. Diffuse gliomas are histopathologically characterized by variably increased cellularity, nuclear pleomorphism and—especially in higher-grade neoplasms—brisk mitotic activity, microvascular proliferation, and necrosis. To visualize these features in live tissue, a technique that elucidates the morphology of tissue is required. In this context, third harmonic generation (THG) microscopy is a promising tool because of its capacity to visualize almost the full morphology of tissue. THG is a nonlinear optical process that relies on spatial variations of the third-order non-linear susceptibility χ⁽³⁾ intrinsic to the tissue and (in the case of brain tissue) mainly arises from interfaces with lipid-rich molecules [17–27]. SHG signals arise from an optical nonlinear process involving non-centrosymmetric molecules present in, for example, microtubules and collagen. THG has been successfully applied to image unstained samples such as insect embryos, plant seeds and intact mammalian tissue [28], epithelial tissues [29–31], zebra fish embryos [32], and the zebra fish nervous system [33]. In brain tissue of mice, augmented by co-recording of SHG signals, THG was shown to visualize cells, nuclei, the inner and outer contours of axons, blood cells, and vessels, resulting in the visualization of both gray and white matter (GM and WM) as well as vascularization, up to a depth of 350 μm [24,26]. Here, we explore the potential of THG and SHG imaging for real time analysis of ex-vivo human brain tissue in the challenging cases of diffuse tumor invasion in low-grade brain tumors as well as of high-grade gliomas and structurally normal brain tissues.

 

Multiphoton imaging

THG and SHG are nonlinear optical processes that may occur in tissue depending on the nonlinear susceptibility coefficients χ⁽³⁾ and χ⁽²⁾ of the tissue and upon satisfying phase matching conditions [17–19,21,23–27]. In the THG process, three incident photons are converted into one photon with triple energy and one third of the wavelength (Fig. 1(A)). In the SHG process, signals result from the conversion of an incident photon pair into one photon with twice the energy and half the wavelength. Two- and three photon excited fluorescence signals (2PF, 3PF) may simultaneously be generated by intrinsic proteins (Fig. 1(B)). As a result, a set of distinct (harmonic) and broadband (autofluorescence) spectral peaks is generated in the visible range. The imaging setup (Fig. 1(C)) to generate and collect these signals consisted of a commercial two-photon laser-scanning microscope (TriMScope I, LaVision BioTec GmbH) and a femtosecond laser source. The laser source was an optical parametric oscillator (Mira-OPO, APE) pumped at 810 nm by a Ti-sapphire oscillator (Coherent Chameleon Ultra II). The OPO generates 200 fs pulses at 1200 nm with a repetition rate of 80 MHz. We selected this wavelength as it falls in the tissue transparency window, providing deeper penetration and reduced photodamage compared to the 700–1000 nm range, as well as harmonic signals generated in the visible wavelength range, facilitating their collection and detection with conventional objectives and detectors. We focused the OPO beam on the sample using a 25 × /1.10 (Nikon APO LWD) water-dipping objective (MO). The 1200 nm beam focal spot size on the sample was d_lateral ~0.7 μm and d_axial ~4.1 μm. It was measured with 0.175 μm fluorescent microspheres (see Section 3.4) yielding two- and three-photon resolution values Δ_2P,lateral ~0.5 μm, Δ_2P,axial ~2.9 μm, Δ_3P,lateral ~0.4 μm, and Δ_3P,axial ~2.4 μm. Two high-sensitivity GaAsP photomultiplier tubes (PMT, Hamamatsu H7422-40) equipped with narrowband filters at 400 nm and 600 nm were used to collect the THG and SHG signals, respectively, as a function of position of the focus in the sample. The signals were filtered from the 1200 nm fundamental photons by a dichroic mirror (Chroma T800LPXRXT, DM1), split into SHG and THG channels by a dichroic mirror (Chroma T425LPXR, DM2), and passed through narrow-band interference filters (F) for SHG (Chroma D600/10X) and THG (Chroma Z400/10X) detection. The efficient back-scattering of the harmonic signals allowed for their detection in epi-direction. The laser beam was transversely scanned over the sample by a pair of galvo mirrors (GM). THG and SHG modalities are intrinsically confocal and therefore provide direct depth sectioning. We obtained a full 3D image of the tissue volume by scanning the microscope objective with a stepper motor in the vertical (z) direction. The mosaic imaging of the sample was performed by transverse (xy) scanning of the motorized translation stage. Imaging data was acquired with the TriMScope I software (“Imspector Pro”); image stacks were stored in 16-bit tiff-format and further processed and analyzed with “ImageJ” software (ver. 1.49m, NIH, USA). All images were processed with logarithmic contrast enhancement.

     http://imagebank.osa.org/getImage.xqy?img=M3cubGFyZ2UsYm9lLTctNS0xODg5LWcwMDE

Fig. 1 THG/SHG microscopy for brain tissue imaging. (A) Energy level diagram of the second (SHG) and third (THG) harmonic generation process. (B) Energy level diagram of the two- (2PF) and three-photon (3PF) excited auto-fluorescence process. (C) Multiphoton microscope setup: Laser producing 200 fs pulses at 1200 nm; GM – X-Y galvo-scanner mirrors; SL – scan lens; TL – tube lens; MO – microscope objective; DM1 – dichroic mirror reflecting back-scattered THG/SHG photons to the PMT detectors; DM2 – dichroic mirror splitting SHG and THG channels; F – narrow-band SHG and THG interference filters; L – focusing lenses; PMT – photomultiplier tube detectors. (D) Infrared photons (white arrow) are focused deep in the brain tissue, converted to THG (green) and SHG (red) photons, scattered back (green/red arrows) and epi-detected. The nonlinear optical processes result in label-free contrast images with sub-cellular resolution and intrinsic depth sectioning. (E and F) Freshly-excised low-grade (E) and high-grade (F) glioma tissue samples in artificial cerebrospinal fluid (ACSF) in a Petri dish with a millimeter paper underneath for scale. (G) An agar-embedded tumor tissue sample under 0.17 mm glass cover slip with the microscope objective (MO) on top.   Download Full Size | PPT Slide

Endomicroscopy imaging

For endomicroscopic imaging we used a commercial high-numerical-aperture (NA) multi-element micro-objective lens (GT-MO-080-018-810, GRINTECH) composed of a plano-convex lens and two GRaded INdex (GRIN) lenses with aberration compensation, object NA = 0.80 and object working distance 200 µm (in water), image NA = 0.18 and image working distance 200 µm (in air), magnification × 4.8 and field-of-view diameter of 200 μm. The GRIN lenses and the plano-convex lens were mounted in a waterproof stainless steel housing with an outer diameter of 1.4 mm and a total length of 7.5 mm. Originally designed for a wavelength range of 800–900 nm [36–41], this micro-objective lens was used for focusing of 1200 nm femtosecond pulses and collection of back-scattered harmonic and fluorescence photons. A coupling lens with f = 40 mm (NA = 0.19, Qioptiq, ARB2 NIR, dia. 25 mm) focused the scanned laser beam in the image plane of the micro-objective lens and forwarded the epi-detected harmonic and fluorescence photons to the PMTs.

We characterized the lateral (x) and axial (z) resolution of the micro-objective lens by 3D imaging of fluorescence microspheres (PS-Speck Microscope Point Source Kit, P7220, Molecular Probes). We used “blue” and “deep red” microspheres, 0.175 ± 0.005 μm in diameter, with excitation/emission maxima at 360/440 nm and 630/660 nm to obtain three-photon (3P) and two-photon (2P) point spread function (PSF) profiles. The excitation wavelength was 1200 nm, and fluorescence signals were detected in the 400 ± 5 nm (3P) and 600 ± 5 nm (2P) spectral windows, just as in the brain tissue imaging experiments. 1 μL of “blue” and “deep red” sphere suspensions were applied to a propanol-cleaned 75 × 26 × 1 mm³ glass slide. The mixed microsphere suspension was left to dry for 20 min and was then imaged with the micro-objective lens via a water immersion layer. The assembly of the coupling lens and the micro-objective lens was vertically (z) scanned with a step of 0.5 μm, and stacks of two-/three-photon images were recorded. The line profiles were then taken over the lateral (xy) images of the fluorescent spheres with maximal intensity (in focus), and fluorescence counts were plotted as function of the lateral coordinate (x). The axial (z) scan values of the two- and three-photon fluorescence signals were acquired by averaging of the total fluorescence counts of the corresponding spheres and were plotted as function of the axial coordinate (z). Lateral (x) and axial (z) 2P/3P points were then fitted with Gaussian functions and full width at half-maximum (FWHM) values were measured.

……. Results….  Conclusions

The results shown here provide the first evidence that—by applying the same microscopic criteria that are used by the pathologist, i.e. increased cellularity, nuclear pleomorphism, and rarefaction of neuropil—THG/SHG ex-vivo microscopy can be used to recognize the presence of diffuse infiltrative glioma in fresh, unstained human brain tissue. Images and a first diagnosis can be provided in seconds, with the ‘inspection mode’, by moving the sample under the scanning microscope (see Visualization 4 and Visualization 5), or in about 5 minutes if an area has to be inspected with sub-cellular detail. The sensitivity of THG to interfaces provides images with excellent contrast in which cell-by-cell variations are visualized. The quality of the images and the speed with which they can be recorded make THG a promising tool for quick assessment of the nature of excised tissue. Importantly, because THG/SHG images are very close to those of histological slides, we expect that the surgeon (or pathologist) will need very little additional training for adequate interpretation of the images. We are planning to construct a THG/SHG ex-vivo tabletop device consisting of a compact laser source and a laser-scanning microscope requiring a physical footprint of only 1 m², to be placed in an operating room, enabling immediate feedback to the surgeon on the nature of excised tissue, during the operation. With this device, we will perform a quantitative study of the added value of rapid THG/SHG pathological feedback during surgery for the final success of the neurosurgery. Finally, we note that THG/SHG imaging does not induce artifacts associated with fixation, freezing, and staining; therefore, tissue fragments examined ex-vivo can still be used for subsequent immunochemical and/or molecular analysis.

The microendoscopy THG/SHG imaging results represent an important step toward the development of a THG/SHG-based bioptic needle, and show that the use of such a needle for in situ optical sampling for optimal resection of gliomas is indeed a viable prospect, as has been demonstrated also before for multi-photon microscopies [38,49–54]. Although there are several issues associated with the operation of a needle-like optical device, such as the fact that blood in the surgical cavity may obscure the view, and the fact that only small areas can be biopsied with a needle, it may be a valuable tool in cases where sparing healthy tissue is of such vital importance as in brain surgery. Therefore, the reasonably good quality of the THG images taken with the GRIN micro-objective shown here, together with the developments in the field of microendoscopy, warrant further development of THG/SHG into a true handheld device. This next step, a true handheld bioptic needle, requires an optical fiber to transport the light from a small footprint laser to the GRIN micro-objective, and a small 2D scanner unit, to enable placing the laser at a sufficient distance from the patient. Patient-safe irradiation levels for THG imaging will have to be determined but are expected to lie in the 10–50 mW range [55–58]. This implies that only minor optimization of signal collection efficiency needs to be achieved, because the images of Fig. 10 were measured with 50 mW incident power.

THG/SHG imaging thus holds great promise for improving surgical procedures, thereby reducing the need for second surgeries and the loss of function by excising non-infiltrated brain tissue, as well as improving survival and quality of life of the patients. In addition, the success in the challenging case of diffuse gliomas promises great potential of THG/SHG-based histological analysis for a much wider spectrum of diagnostic applications.

References and links

1. N. G. Burnet, S. J. Jefferies, R. J. Benson, D. P. Hunt, and F. P. Treasure, “Years of life lost (YLL) from cancer is an important measure of population burden–and should be considered when allocating research funds,” Br. J. Cancer 92(2), 241–245 (2005). [PubMed]  

2. J. A. Schwartzbaum, J. L. Fisher, K. D. Aldape, and M. Wrensch, “Epidemiology and molecular pathology of glioma,” Nat. Clin. Pract. Neurol. 2(9), 494–516 (2006). [CrossRef]   [PubMed]  

3. J. S. Smith, E. F. Chang, K. R. Lamborn, S. M. Chang, M. D. Prados, S. Cha, T. Tihan, S. Vandenberg, M. W. McDermott, and M. S. Berger, “Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas,” J. Clin. Oncol. 26(8), 1338–1345 (2008). [CrossRef]   [PubMed]  

4. N. Sanai and M. S. Berger, “Glioma extent of resection and its impact on patient outcome,” Neurosurgery 62(4), 753–766 (2008). [CrossRef]   [PubMed]  

5. I. Y. Eyüpoglu, M. Buchfelder, and N. E. Savaskan, “Surgical resection of malignant gliomas-role in optimizing patient outcome,” Nat. Rev. Neurol. 9(3), 141–151 (2013). [CrossRef]  [PubMed]  

6. U. Pichlmeier, A. Bink, G. Schackert, and W. Stummer, “Resection and survival in glioblastoma multiforme: An RTOG recursive partitioning analysis of ALA study patients,” Neuro-oncol. 10(6), 1025–1034 (2008). [CrossRef]   [PubMed]  

7. W. Stummer, J. C. Tonn, C. Goetz, W. Ullrich, H. Stepp, A. Bink, T. Pietsch, and U. Pichlmeier, “5-Aminolevulinic Acid-Derived Tumor Fluorescence: The Diagnostic Accuracy of Visible Fluorescence Qualities as Corroborated by Spectrometry and Histology and Postoperative Imaging,” Neurosurgery 74(3), 310–320 (2014). [CrossRef]   [PubMed]  

….. more

Tables (1)

Table 1 Pre-operative diagnoses and cell densities observed in the studied brain tissue samples by THG imaging and corresponding H&E histopathology.

View Table

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

GE’s large scale 3D cookbook

Posted in 3D Plotting Scaffolds, 3D Printing for Medical Application, tagged 3D printing, GE, GE global research on April 13, 2016| Leave a Comment »

GE’s large scale 3D cookbook

Curator: Larry H. Bernstein, MD, FCAP

 

 

Major Laser: These Scientists Are Writing the 3D-Printing Cookbook for GE

Wed, 04/13/2016 – 10:05amby Todd Alhart, GE Reports

http://www.pharmpro.com/news/2016/04/major-laser-these-scientists-are-writing-3d-printing-cookbook-ge

http://www.pharmpro.com/sites/pharmpro.com/files/styles/content_body_image/public/embedded_image/2016/04/Major%20Laser_GE%20Reports_1.jpg?itok=gFQswoU8

Additive manufacturing engineer Brian Adkins in full gear is preparing a DMLM machine for printing. (Photo credit: GE Reports/Chris New)

It would be a stretch to say that Joe Vinciquerra is the Julia Child of GE. But Vinciquerra, the manager of the newly formed Additive Materials Lab at GE Global Research, is creating a cookbook that will likely impact manufacturing across GE the same way “Mastering the Art of French Cooking” shook up American kitchens.

Additive manufacturing, commonly known as 3D printing, is exploding right now. GE estimates that by 2025, more than 20 percent of new products will involve additive processes of some kind. But there’s no cookbook that standardizes the recipes, which have oodles of parameters that determine the properties of the final part.

“It’s like baking a cake. You need to start with the right recipe, then you need to have the right ingredients and the right oven,” Vinciquerra says. “A cup of materials science, a tablespoon of design and a whole lot of machine-control strategies must come together and yield perfection.”

Technologies like direct metal laser melting (DMLM), for example, can involve several lasers as powerful as 1 kilowatt—enough to burn a hole in a wall—fusing as many as 1,250 layers of fine superalloy powder into the desired shape. Some large builds can take days to finish.

http://www.pharmpro.com/sites/pharmpro.com/files/styles/content_body_image/public/embedded_image/2016/04/Major%20Laser_GE%20Reports_2.jpg?itok=X_3HxAyF

support block with 3D printed parts inside a DMLM printed in Pittsburgh. (Photo credit: GE Reports/Chris New)

Last week, GE opened a new industrial-scale 3D-printing center in Pittsburgh, Pennsylvania. It will work closely with Vinciquerra’s team, test their findings and get GE factories quickly cooking with additive.

His team has already started testing and tabling the powdered materials used in additive manufacturing and their properties. “We want to know how they come together, how they affect each other and what machines and processes are best suited for them,” Vinciquerra says. “It’s just like a gourmet recipe. We need to know how our ingredients are going to react in a mixer or an oven. And what changes can we make to those ingredients, the mixer or the oven to produce a more palatable dish?”

The team is pulling in expertise from other labs on the GE Global Research campus in Niskayuna, New York, including scientists focusing on nanomaterials, microstructures and machine design. The company calls the cross-pollination of know-how the GE Store.

inciquerra (right) and Andy Deal, a metallurgist in the Additive Materials Lab are loading sets of sample 3D printed metal parts in a vacuum oven for post-processing at GE Global Research. (Photo credit: GE Global Research.)      http://www.pharmpro.com/sites/pharmpro.com/files/styles/content_body_image/public/embedded_image/2016/04/Major%20Laser_GE%20Reports_3.jpg?itok=GSQMNM4L

 

GE materials scientists are no strangers to new materials. They spent two decades developing light- and heat-resistant materials called ceramic matrix composites that outperform even the most advanced superalloys and make jet engines and gas turbines lighter and more efficient. But additive materials live in a different universe. “With additive, you can design as you go and create architectures that cannot be manufactured by any other means,” Vinciquerra says.

He says that GE engineers can already design components with sophisticated, performance-enhancing features previously unattainable by any other means of manufacturing. The next-generation LEAP jet engine—developed by CFM International, a joint venture between GE Aviation and France’s Snecma (Safran)—uses 3D-printed fuel nozzles, which are 25 percent lighter and five times more durable. They used to be made from 18 separate parts and now they come in one piece. A year ago, the Federal Aviation Administration (FAA) approved a fist-sized housing for a sensor as the first 3D-printed part to fly inside GE commercial jet engines.

“This is just the beginning,” Vinciquerra says. “Someday, we may even be able to combine materials together in ways previously not possible to unlock new capabilities that never existed. Can I create a new class of materials that open the design envelope and push the limits of durability and heat resistance beyond what we thought was even possible? We’re going to find out.”

To read the original story, published on GE Reports, click here! 

 

 

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

3D revolution and tissue repair

Posted in 3D Plotting Scaffolds, Bio Instrumentation in Experimental Life Sciences Research, BioInks, BioPrinting in Regenerative Medicine, Chemical Biology and its relations to Metabolic Disease, Clinical & Translational, Curation, Genome Biology, Medical Devices R&D and Inventions, Specialized 3D BioPrinters (Cornea, Stem Cells for Regenerative Medicine, tagged 3D printing, cell plasticity, coralyne-induced spatial asymmetry, DNA nanostructures, DNA-nanogold conjugates, electron tomography, electron transport, induced multipotent stem cells (iMS), nanocrystal-based field effect transistors, stem cells, tissue engineering scaffolds, tissue repair on April 11, 2016| Leave a Comment »

3D revolution and tissue repair

Curator: Larry H. Bernstein, MD, FCAP

 

 

Berkeley Lab captures first high-res 3D images of DNA segments

DNA segments are targeted to be building blocks for molecular computer memory and electronic devices, nanoscale drug-delivery systems, and as markers for biological research and imaging disease-relevant proteins

www.kurzweilai.net/berkeley-lab-captures-first-high-res-3d-images-of-dna-segments

http://www.kurzweilai.net/images/Cover-fig-512×461.png

In a Berkeley Lab-led study, flexible double-helix DNA segments (purple, with green DNA models) connected to gold nanoparticles (yellow) are revealed from the 3D density maps reconstructed from individual samples using a Berkeley Lab-developed technique called individual-particle electron tomography (IPET). Projections of the structures are shown in the green background grid. (credit: Berkeley Lab)

An international research team working at the Lawrence Berkeley National Laboratory (Berkeley Lab) has captured the first high-resolution 3D images of double-helix DNA segments attached at either end to gold nanoparticles — which could act as building blocks for molecular computer memory and electronic devices (see World’s smallest electronic diode made from single DNA molecule), nanoscale drug-delivery systems, and as markers for biological research and for imaging disease-relevant proteins.

The researchers connected coiled DNA strands between polygon-shaped gold nanoparticles and then reconstructed 3D images, using a cutting-edge electron microscope technique coupled with a protein-staining process and sophisticated software that provided structural details at the scale of about 2 nanometers.

“We had no idea about what the double-strand DNA would look like between the gold nanoparticles,” said Gang “Gary” Ren, a Berkeley Lab scientist who led the research. “This is the first time for directly visualizing an individual double-strand DNA segment in 3D,” he said.

The results were published in an open-access paper in the March 30 edition of Nature Communications.

The method developed by this team, called individual-particle electron tomography (IPET), had earlier captured the 3-D structure of a single protein that plays a key role in human cholesterol metabolism. By grabbing 2D images of an object from different angles, the technique allows researchers to assemble a 3D image of that object.

The team has also used the technique to uncover the fluctuation of another well-known flexible protein, human immunoglobulin 1, which plays a role in the human immune system.

https://youtu.be/lQrbmg9ry90
Berkeley Lab | 3-D Reconstructions of Double strand DNA and Gold Nanoparticle Structures

For this new study of DNA nanostructures, Ren used an electron-beam study technique called cryo-electron microscopy (cryo-EM) to examine frozen DNA-nanogold samples, and used IPET to reconstruct 3-D images from samples stained with heavy metal salts. The team also used molecular simulation tools to test the natural shape variations (“conformations”) in the samples, and compared these simulated shapes with observations.

First visualization of DNA strand dynamics without distorting x-ray crystallography

Ren explained that the naturally flexible dynamics of samples, like a man waving his arms, cannot be fully detailed by any method that uses an average of many observations.

A popular way to view the nanoscale structural details of delicate biological samples is to form them into crystals and zap them with X-rays, but that destroys their natural shape, especially fir the DNA-nanogold samples in this study, which the scientists say are incredibly challenging to crystallize. Other common research techniques may require a collection of thousands of near-identical objects, viewed with an electron microscope, to compile a single, averaged 3-D structure. But an averaged 3D image may not adequately show the natural shape fluctuations of a given object.

The samples in the latest experiment were formed from individual polygon gold nanostructures, measuring about 5 nanometers across, connected to single DNA-segment strands with 84 base pairs. Base pairs are basic chemical building blocks that give DNA its structure. Each individual DNA segment and gold nanoparticle naturally zipped together with a partner to form the double-stranded DNA segment with a gold particle at either end.

https://youtu.be/RDOpgj62PLU
Berkeley Lab | These views compare the various shape fluctuations obtained from different samples of the same type of double-helix DNA segment (DNA renderings in green, 3D reconstructions in purple) connected to gold nanoparticles (yellow).

The samples were flash-frozen to preserve their structure for study with cryo-EM imaging. The distance between the two gold nanoparticles in individual samples varied from 20 to 30 nanometers, based on different shapes observed in the DNA segments.

Researchers used a cryo-electron microscope at Berkeley Lab’s Molecular Foundry for this study. They collected a series of tilted images of the stained objects, and reconstructed 14 electron-density maps that detailed the structure of individual samples using the IPET technique.

Sub-nanometer images next

Ren said that the next step will be to work to improve the resolution to the sub-nanometer scale.

“Even in this current state we begin to see 3-D structures at 1- to 2-nanometer resolution,” he said. “Through better instrumentation and improved computational algorithms, it would be promising to push the resolution to that visualizing a single DNA helix within an individual protein.”

In future studies, researchers could attempt to improve the imaging resolution for complex structures that incorporate more DNA segments as a sort of “DNA origami,” Ren said. Researchers hope to build and better characterize nanoscale molecular devices using DNA segments that can, for example, store and deliver drugs to targeted areas in the body.

“DNA is easy to program, synthesize and replicate, so it can be used as a special material to quickly self-assemble into nanostructures and to guide the operation of molecular-scale devices,” he said. “Our current study is just a proof of concept for imaging these kinds of molecular devices’ structures.”

The team included researchers at UC Berkeley, the Kavli Energy NanoSciences Institute at Berkeley Lab and UC Berkeley, and Xi’an Jiaotong University in China. This work was supported by the National Science Foundation, DOE Office of Basic Energy Sciences, National Institutes of Health, the National Natural Science Foundation of China, Xi’an Jiaotong University in China, and the Ministry of Science and Technology in China. View more about Gary Ren’s research group here.

---

Abstract of Three-dimensional structural dynamics and fluctuations of DNA-nanogold conjugates by individual-particle electron tomography

DNA base pairing has been used for many years to direct the arrangement of inorganic nanocrystals into small groupings and arrays with tailored optical and electrical properties. The control of DNA-mediated assembly depends crucially on a better understanding of three-dimensional structure of DNA-nanocrystal-hybridized building blocks. Existing techniques do not allow for structural determination of these flexible and heterogeneous samples. Here we report cryo-electron microscopy and negative-staining electron tomography approaches to image, and three-dimensionally reconstruct a single DNA-nanogold conjugate, an 84-bp double-stranded DNA with two 5-nm nanogold particles for potential substrates in plasmon-coupling experiments. By individual-particle electron tomography reconstruction, we obtain 14 density maps at ~2-nm resolution. Using these maps as constraints, we derive 14 conformations of dsDNA by molecular dynamics simulations. The conformational variation is consistent with that from liquid solution, suggesting that individual-particle electron tomography could be an expected approach to study DNA-assembling and flexible protein structure and dynamics.

references:

• Gang Ren et al. Three-dimensional structural dynamics and fluctuations of DNA-nanogold conjugates by individual-particle electron tomography. Nature Communications, March 2016 DOI: 10.1038/ncomms11083 (open access)

 

World’s smallest electronic diode made from single DNA molecule

Electronic components 1,000 times smaller than with silicon may be possible
http://www.kurzweilai.net/worlds-smallest-electronic-diode-made-from-single-dna-molecule

http://www.kurzweilai.net/images/DNA-diode.jpg

By inserting a small “coralyne” molecule into DNA, scientists were able to create a single-molecule diode (connected here by two gold electrodes), which can be used as an active element in future nanoscale circuits. The diode circuit symbol is shown on the left. (credit: University of Georgia and Ben-Gurion University)

Nanoscale electronic components can be made from single DNA molecules, as researchers at the University of Georgia and at Ben-Gurion University in Israel have demonstrated, using a single molecule of DNA to create the world’s smallest diode.

DNA double helix with base pairs (credit: National Human Genome Research Institute)

A diode is a component vital to electronic devices that allows current to flow in one direction but prevents its flow in the other direction. The development could help stimulate development of DNA components for molecular electronics.

As noted in an open-access Nature Chemistry paper published this week, the researchers designed a 11-base-pair (bp) DNA molecule and inserted a small molecule named coralyne into the DNA.*

They found, surprisingly, that this caused the current flowing through the DNA to be 15 times stronger for negative voltages than for positive voltages, a necessary feature of a diode.

Electronic elements 1,00o times smaller than current components

“Our discovery can lead to progress in the design and construction of nanoscale electronic elements that are at least 1,000 times smaller than current components,” says the study’s lead author, Bingqian Xu an associate professor in the UGA College of Engineering and an adjunct professor in chemistry and physics.

The research team plans to enhance the performance of the molecular diode and construct additional molecular devices, which may include a transistor (similar to a two-layer diode, but with one additional layer).

A theoretical model developed by Yanantan Dubi of Ben-Gurion University indicated the diode-like behavior of DNA originates from the bias voltage-induced breaking of spatial symmetry inside the DNA molecule after the coralyne is inserted.

The research is supported by the National Science Foundation.

*“We prepared the DNA–coralyne complex by specifically intercalating two coralyne molecules into a custom-designed 11-base-pair (bp) DNA molecule (5′-CGCGAAACGCG-3′) containing three mismatched A–A base pairs at the centre,” according to the authors.

UPDATE April 6, 2016 to clarify the coralyne intercalation (insertion) into the DNA molecule.

---

Abstract of Molecular rectifier composed of DNA with high rectification ratio enabled by intercalation

The predictability, diversity and programmability of DNA make it a leading candidate for the design of functional electronic devices that use single molecules, yet its electron transport properties have not been fully elucidated. This is primarily because of a poor understanding of how the structure of DNA determines its electron transport. Here, we demonstrate a DNA-based molecular rectifier constructed by site-specific intercalation of small molecules (coralyne) into a custom-designed 11-base-pair DNA duplex. Measured current–voltage curves of the DNA–coralyne molecular junction show unexpectedly large rectification with a rectification ratio of about 15 at 1.1 V, a counter-intuitive finding considering the seemingly symmetrical molecular structure of the junction. A non-equilibrium Green’s function-based model—parameterized by density functional theory calculations—revealed that the coralyne-induced spatial asymmetry in the electron state distribution caused the observed rectification. This inherent asymmetry leads to changes in the coupling of the molecular HOMO−1 level to the electrodes when an external voltage is applied, resulting in an asymmetric change in transmission.

references:

• Cunlan Guo, Kun Wang, Elinor Zerah-Harush, Joseph Hamill, Bin Wang, Yonatan Dubi, Bingqian Xu. Molecular rectifier composed of DNA with high rectification ratio enabled by intercalation. Nature Chemistry, 2016; DOI: 10.1038/nchem.2480
• Cunlan Guo, Kun Wang, Elinor Zerah-Harush, Joseph Hamill, Bin Wang, Yonatan Dubi, Bingqian Xu. Molecular rectifier composed of DNA with high rectification ratio enabled by intercalation. Nature Chemistry, 2016; Supplementary Information (open access)

related:

• A high-performance single-molecule diode

 

A stem-cell repair system that can regenerate any kind of human tissue …including disease and aging; human trials next year
http://www.kurzweilai.net/a-stem-cell-repair-system-that-can-regenerate-any-kind-of-human-tissue

http://www.kurzweilai.net/images/spinal_disc_regeneration.jpg

UNSW researchers say the therapy has enormous potential for treating spinal disc injury and joint and muscle degeneration and could also speed up recovery following complex surgeries where bones and joints need to integrate with the body (credit: UNSW TV)

A stem cell therapy system capable of regenerating any human tissue damaged by injury, disease, or aging could be available within a few years, say University of New South Wales (UNSW Australia) researchers.

Their new repair system*, similar to the method used by salamanders to regenerate limbs, could be used to repair everything from spinal discs to bone fractures, and could transform current treatment approaches to regenerative medicine.

The UNSW-led research was published this week in the Proceedings of the National Academy of Sciences journal.

Reprogramming bone and fat cells

The system reprograms bone and fat cells into induced multipotent stem cells (iMS), which can regenerate multiple tissue types and has been successfully demonstrated in mice, according to study lead author, haematologist, and UNSW Associate Professor John Pimanda.

“This technique is a significant advance on many of the current unproven stem cell therapies, which have shown little or no objective evidence they contribute directly to new tissue formation,” Pimanda said. “We have taken bone and fat cells, switched off their memory and converted them into stem cells so they can repair different cell types once they are put back inside the body.”

“We are currently assessing whether adult human fat cells reprogrammed into iMS cells can safely repair damaged tissue in mice, with human trials expected to begin in late 2017.”

http://www.kurzweilai.net/images/UNSW-stem-cell-repair.jpg

Advantages over stem-cell types

There are different types of stem cells including embryonic stem (ES) cells, which during embryonic development generate every type of cell in the human body, and adult stem cells, which are tissue-specific, but don’t regenerate multiple tissue types. Embryonic stem cells cannot be used to treat damaged tissues because of their tumor forming capacity. The other problem when generating stem cells is the requirement to use viruses to transform cells into stem cells, which is clinically unacceptable, the researchers note.

Research shows that up to 20% of spinal implants either don’t heal or there is delayed healing. The rates are higher for smokers, older people and patients with diseases such diabetes or kidney disease.

Human trials are planned next year once the safety and effectiveness of the technique using human cells in mice has been demonstrated.

* The technique involves extracting adult human fat cells and treating them with the compound 5-Azacytidine (AZA), along with platelet-derived growth factor-AB (PDGF-AB) for about two days. The cells are then treated with the growth factor alone for a further two-three weeks.

AZA is known to induce cell plasticity, which is crucial for reprogramming cells. The AZA compound relaxes the hard-wiring of the cell, which is expanded by the growth factor, transforming the bone and fat cells into iMS cells. When the stem cells are inserted into the damaged tissue site, they multiply, promoting growth and healing.

The new technique is similar to salamander limb regeneration, which is also dependent on the plasticity of differentiated cells, which can repair multiple tissue types, depending on which body part needs replacing.

Along with confirming that human adult fat cells reprogrammed into iMS stem cells can safely repair damaged tissue in mice, the researchers said further work is required to establish whether iMS cells remain dormant at the sites of transplantation and retain their capacity to proliferate on demand.

https://youtu.be/zAMCBNujzzw

Abstract of PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells

Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to a receptive growth factor might result in the expansion of a plastic and proliferative population of cells. To this end, we treated lineage-committed cells with AZA and screened a number of different growth factors with known activity in mesenchyme-derived tissues. Here, we report that transient treatment with AZA in combination with platelet-derived growth factor–AB converts primary somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells possess a distinct transcriptome, are immunosuppressive, and demonstrate long-term self-renewal, serial clonogenicity, and multigerm layer differentiation potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner and, unlike embryonic or pluripotent stem cells, do not form teratomas. Taken together, this vector-free method of generating iMS cells from primary terminally differentiated cells has significant scope for application in tissue regeneration.

references:

• Vashe Chandrakanthan, Avani Yeola, Jair C. Kwan, Rema A. Oliver, Qiao Qiao, …, William Walsh, and John E. Pimanda.  PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells. PNAS, April 4, 2016 DOI: 10.1073/pnas.1518244113

related:

• Scientists time-reverse developed stem cells to make them ‘embryonic’ again
• Could humans ever regenerate limbs?

 

First transistors made entirely of nanocrystal ‘inks’ in simplified process

Transistors and other electronic components to be built into flexible or wearable applications; 3D printing planned
http://www.kurzweilai.net/first-transistors-made-entirely-of-nanocrystal-inks

http://www.kurzweilai.net/images/Flexible-Transistors-.jpg

Because this process works at relatively low temperatures, many transistors can be made on a flexible backing at once. (credit: University of Pennsylvania)

University of Pennsylvania engineers have developed a simplified new approach for making transistors by sequentially depositing their components in the form of liquid nanocrystal “inks.” The new process open the door for transistors and other electronic components to be built into flexible or wearable applications. It also avoids the highly complex current process for creating transistors, which requires high-temperature, high-vacuum equipment. Also, the new lower-temperature process is compatible with a wide array of materials and can be applied to larger areas.

Transistors patterned on plastic backing

The researchers’ nanocrystal-based field effect transistors were patterned onto flexible plastic backings using spin coating, but could eventually be constructed by additive manufacturing systems, like 3D printers.

Published in the journal Science,  the study was lead by Cherie Kagan, the Stephen J. Angello Professor in the School of Engineering and Applied Science, and Ji-Hyuk Choi, then a member of her lab, now a senior researcher at the Korea Institute of Geoscience and Mineral Resources. Researchers at Korea University Korea’s Yonsei University were also involved.

[+]

Kagan’s group developed four nanocrystal inks that comprise the transistor, then deposited them on a flexible backing. (credit: University of Pennsylvania)

The researchers began by dispersing a specific type of nanocrystals in a liquid, creating nanocrystal inks. They developed a library of four of these inks: a conductor (silver), an insulator (aluminum oxide), a semiconductor (cadmium selenide), and a conductor combined with a dopant (a mixture of silver and indium). (“Doping” the semiconductor layer of a transistor with impurities controls whether the device creates a positive or negative charge.)

“These materials are colloids just like the ink in your inkjet printer,” Kagan said, “but you can get all the characteristics that you want and expect from the analogous bulk materials, such as whether they’re conductors, semiconductors or insulators.” Although the electrical properties of several of these nanocrystal inks had been independently verified, they had never been combined into full devices. “Our question was whether you could lay them down on a surface in such a way that they work together to form functional transistors.”

Laying down patterns in layers

Such a process entails layering or mixing them in precise patterns.

First, the conductive silver nanocrystal ink was deposited from liquid on a flexible plastic surface that was treated with a photolithographic mask, then rapidly spun to draw it out in an even layer. The mask was then removed to leave the silver ink in the shape of the transistor’s gate electrode.

The researchers followed that layer by spin-coating a layer of the aluminum oxide nanocrystal-based insulator, then a layer of the cadmium selenide nanocrystal-based semiconductor and finally another masked layer for the indium/silver mixture, which forms the transistor’s source and drain electrodes. Upon heating at relatively low temperatures, the indium dopant diffused from those electrodes into the semiconductor component.

“The trick with working with solution-based materials is making sure that, when you add the second layer, it doesn’t wash off the first, and so on,” Kagan said. “We had to treat the surfaces of the nanocrystals, both when they’re first in solution and after they’re deposited, to make sure they have the right electrical properties and that they stick together in the configuration we want.”

Because this entirely ink-based fabrication process works at lower temperatures than existing vacuum-based methods, the researchers were able to make several transistors on the same flexible plastic backing at the same time.

[+]

The inks’ specialized surface chemistry allowed them to stay in configuration without losing their electrical properties. (credit: University of Pennsylvania)

“Making transistors over larger areas and at lower temperatures have been goals for an emerging class of technologies, when people think of the Internet of things, large area flexible electronics and wearable devices,” Kagan said. “We haven’t developed all of the necessary aspects so they could be printed yet, but because these materials are all solution-based, it demonstrates the promise of this materials class and sets the stage for additive manufacturing.”

Because this entirely ink-based fabrication process works at lower temperatures than existing vacuum-based methods, the researchers were able to make several transistors on the same flexible plastic backing at the same time.

3D-printing transistors for wearables

“This is the first work,” Choi said, “showing that all the components, the metallic, insulating, and semiconducting layers of the transistors, and even the doping of the semiconductor, could be made from nanocrystals.”

“Making transistors over larger areas and at lower temperatures have been goals for an emerging class of technologies, when people think of the Internet of things, large area flexible electronics and wearable devices,” Kagan said. “We haven’t developed all of the necessary aspects so they could be printed yet, but because these materials are all solution-based, it demonstrates the promise of this materials class and sets the stage for additive manufacturing.”

The research was supported by the National Science Foundation, the U.S. Department of Energy, the Office of Naval Research, and the Korea Institute of Geoscience and Mineral Resources funded by the Ministry of Science, ICT, and Future Planning of Korea.

---

Abstract of Exploiting the colloidal nanocrystal library to construct electronic devices

Synthetic methods produce libraries of colloidal nanocrystals with tunable physical properties by tailoring the nanocrystal size, shape, and composition. Here, we exploit colloidal nanocrystal diversity and design the materials, interfaces, and processes to construct all-nanocrystal electronic devices using solution-based processes. Metallic silver and semiconducting cadmium selenide nanocrystals are deposited to form high-conductivity and high-mobility thin-film electrodes and channel layers of field-effect transistors. Insulating aluminum oxide nanocrystals are assembled layer by layer with polyelectrolytes to form high–dielectric constant gate insulator layers for low-voltage device operation. Metallic indium nanocrystals are codispersed with silver nanocrystals to integrate an indium supply in the deposited electrodes that serves to passivate and dope the cadmium selenide nanocrystal channel layer. We fabricate all-nanocrystal field-effect transistors on flexible plastics with electron mobilities of 21.7 square centimeters per volt-second.

references:

• Ji-Hyuk Choi, Han Wang, Soong Ju Oh, Taejong Paik, …., Christopher B. Murray, Cherie R. Kagan. Exploiting the colloidal nanocrystal library to construct electronic devices. Science, 08 Apr 2016 DOI: 10.1126/science.aad0371

Best textile manufacturing methods for creating human tissues with stem cells

Bioengineers determine three best processes for engineering tissues needed for organ and tissue repair
http://www.kurzweilai.net/best-textile-manufacturing-methods-for-creating-human-tissues-with-stem-cells

http://www.kurzweilai.net/images/tissue-scaffolds.jpg

All four textile manufacturing processes and corresponding scaffold (structure) types studied exhibited the presence of lipid vacuoles (small red spheres, right column, indicating stem cells undergoing random differentiation), compared to control (left). Electrospun scaffolds (row a) exhibited only a monolayer of lipid vacuoles in a single focal plane, while meltblown, spunbond, and carded scaffolds (rows b, c, d) exhibited vacuoles in multiple planes throughout the fabric thickness. Scale bars: 100 μm (credit: S. A. Tuin et al./Biomedical Materials)

Elizabeth Loboa, dean of the Missouri University College of Engineering, and her team have tested new tissue- engineering methods (based on textile manufacturing) to find ones that are most cost-effective and can be produced in larger quantities.

Tissue engineering is a process that uses novel biomaterials seeded with stem cells to grow and replace missing tissues. When certain types of materials are used, the “scaffolds” that are created to hold stem cells eventually degrade, leaving natural tissue in its place. The new tissues could help patients suffering from wounds caused by diabetes and circulation disorders, patients in need of cartilage or bone repair, and women who have had mastectomies by replacing their breast tissue. The challenge is creating enough of the material on a scale that clinicians need to treat patients.

Comparing textile manufacturing techniques

http://www.kurzweilai.net/images/electrospinning.png

Electrospinning experiment: nanofibers are collected into an ethanol bath and removed at predefined time intervals (credit: J. M. Coburn et al./The Johns Hopkins University/PNAS)

In typical tissue engineering approaches that use fibers as scaffolds, non-woven materials are often bonded together using an electrostatic field. This process, called electrospinning (see Nanoscale scaffolds and stem cells show promise in cartilage repair and Improved artificial blood vessels), creates the scaffolds needed to attach to stem cells.

However, large-scale production with electrospinning is not cost-effective. “Electrospinning produces weak fibers, scaffolds that are not consistent, and pores that are too small,” Loboa said. “The goal of ‘scaling up’ is to produce hundreds of meters of material that look the same, have the same properties, and can be used in clinical settings. So we investigated the processes that create textiles, such as clothing and window furnishings like drapery, to scale up the manufacturing process.”

The group published two papers using three industry-standard, high-throughput manufacturing techniques — meltblowing, spunbonding, and carding — to determine if they would create the materials needed to mimic native tissue.

Meltblowing is a technique during which nonwoven materials are created using a molten polymer to create continuous fibers. Spunbond materials are made much the same way but the fibers are drawn into a web while in a solid state instead of a molten one. Carding involves the separation of fibers through the use of rollers, forming the web needed to hold stem cells in place.

http://www.kurzweilai.net/images/carded-scaffold-fabrication.jpg

Schematic of gilled fiber multifilament spinning and carded scaffold fabrication (credit: Stephen A. Tuin et al./Acta Biomaterialia)

Cost-effective methods

Loboa and her colleagues tested these techniques to create polylactic acid (PLA) scaffolds (a Food and Drug Administration-approved material used as collagen fillers), seeded with human stem cells. They then spent three weeks studying whether the stem cells remained healthy and if they began to differentiate into fat and bone pathways, which is the goal of using stem cells in a clinical setting when new bone and/or new fat tissue is needed at a defect site. Results showed that the three textile manufacturing methods proved as viable if not more so than electrospinning.

“These alternative methods are more cost-effective than electrospinning,” Loboa said. “A small sample of electrospun material could cost between $2 to $5. The cost for the three manufacturing methods is between $.30 to $3.00; these methods proved to be effective and efficient. Next steps include testing how the different scaffolds created in the three methods perform once implanted in animals.”

Researchers at North Carolina State University and the University of North Carolina at Chapel Hill were also involved in the two studies, which were published in Biomedical Materials (open access) and Acta Biomaterialia. The National Science Foundation, the National Institutes of Health, and the Nonwovens Institute provided funding for the studies.

---

Abstract of Creating tissues from textiles: scalable nonwoven manufacturing techniques for fabrication of tissue engineering scaffolds

Electrospun nonwovens have been used extensively for tissue engineering applications due to their inherent similarities with respect to fibre size and morphology to that of native extracellular matrix (ECM). However, fabrication of large scaffold constructs is time consuming, may require harsh organic solvents, and often results in mechanical properties inferior to the tissue being treated. In order to translate nonwoven based tissue engineering scaffold strategies to clinical use, a high throughput, repeatable, scalable, and economic manufacturing process is needed. We suggest that nonwoven industry standard high throughput manufacturing techniques (meltblowing, spunbond, and carding) can meet this need. In this study, meltblown, spunbond and carded poly(lactic acid) (PLA) nonwovens were evaluated as tissue engineering scaffolds using human adipose derived stem cells (hASC) and compared to electrospun nonwovens. Scaffolds were seeded with hASC and viability, proliferation, and differentiation were evaluated over the course of 3 weeks. We found that nonwovens manufactured via these industry standard, commercially relevant manufacturing techniques were capable of supporting hASC attachment, proliferation, and both adipogenic and osteogenic differentiation of hASC, making them promising candidates for commercialization and translation of nonwoven scaffold based tissue engineering strategies.

---

Abstract of Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering applications

The fabrication and characterization of novel high surface area hollow gilled fiber tissue engineering scaffolds via industrially relevant, scalable, repeatable, high speed, and economical nonwoven carding technology is described. Scaffolds were validated as tissue engineering scaffolds using human adipose derived stem cells (hASC) exposed to pulsatile fluid flow (PFF). The effects of fiber morphology on the proliferation and viability of hASC, as well as effects of varied magnitudes of shear stress applied via PFF on the expression of the early osteogenic gene marker runt related transcription factor 2 (RUNX2) were evaluated. Gilled fiber scaffolds led to a significant increase in proliferation of hASC after seven days in static culture, and exhibited fewer dead cells compared to pure PLA round fiber controls. Further, hASC-seeded scaffolds exposed to 3 and 6 dyn/cm² resulted in significantly increased mRNA expression of RUNX2 after one hour of PFF in the absence of soluble osteogenic induction factors. This is the first study to describe a method for the fabrication of high surface area gilled fibers and scaffolds. The scalable manufacturing process and potential fabrication across multiple nonwoven and woven platforms makes them promising candidates for a variety of applications that require high surface area fibrous materials.

Statement of Significance

We report here for the first time the successful fabrication of novel high surface area gilled fiber scaffolds for tissue engineering applications. Gilled fibers led to a significant increase in proliferation of human adipose derived stem cells after one week in culture, and a greater number of viable cells compared to round fiber controls. Further, in the absence of osteogenic induction factors, gilled fibers led to significantly increased mRNA expression of an early marker for osteogenesis after exposure to pulsatile fluid flow. This is the first study to describe gilled fiber fabrication and their potential for tissue engineering applications. The repeatable, industrially scalable, and versatile fabrication process makes them promising candidates for a variety of scaffold-based tissue engineering applications.

references:

• S A Tuin, B Pourdeyhimi, E G Loboa. Creating tissues from textiles: scalable nonwoven manufacturing techniques for fabrication of tissue engineering scaffolds. Biomedical Materials, 2016; 11 (1): 015017 DOI: 10.1088/1748-6041/11/1/015017 (open access)
• Stephen A. Tuin, Behnam Pourdeyhimi, Elizabeth G. Loboa. Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering applications. Acta Biomaterialia, 2016; DOI: 10.1016/j.actbio.2016.03.025

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

A step forward in diagnostics

Posted in 3D Plotting Scaffolds, tagged 3D biological structure, optical images, Pathology, Radiology on April 8, 2016| Leave a Comment »

A step forward in diagnostics

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

3D Imaging of Cancer Cells Could Lead to Improved Ability of Pathologists and Radiologists to Plan Cancer Treatments and Monitor Cell Interactions

DARK DAILY   4/8/2016   info@DarkDaily.com  http://www.darkdaily.com/#axzz45En6Xbfr

 

Imaging research is one step closer to giving clinicians a way to do high-resolution scans of malignant cells in order to diagnose cancer and help identify useful therapies. If this technology were to prove successful in clinical studies, it might change how anatomic pathologists and radiologists diagnose and treat cancer.

Researchers at the University of Texas Southwestern Medical Center developed a way to create near-isotropic, high-resolution scans of cells within their microenvironments. The process involves utilizing a combination of two-photonBessel beams and specialized filtering.

New Imaging Approach Could be Useful to Both Pathologists and Radiologists

In a recent press release, senior author Reto Fiolka, PhD, said “there is clear evidence that the environment strongly affects cellular behavior—thus, the value of cell culture experiments on glass must at least be questioned. Our microscope is one tool that may bring us a deeper understanding of the molecular mechanisms that drive cancer cell behavior, since it enables high-resolution imaging in more realistic tumor.”

In a study in Developmental Cell, Erik S. Welf, PhD, et al, described the new microenvironmental selective plane illumination microscopy (meSPIM). When developing the technology, the team outlined three goals:

1. The microscope design must not prohibitively constrain microenvironmental properties.

2. Spatial and temporal resolution must match the cellular features of interest.

3. Spatial resolution must be isotropic to avoid spatial bias in quantitative measurements.

This new technology offers pathologists and medical laboratory scientists a new look at cancer cells and other diseases. The study notes that meSPIM eliminates the influence of stiff barriers, such as glass slide covers, while also allowing a level of control over both mechanical and chemical influences that was previously impossible.

Early meSPIM Research Reveals New Cell Behaviors

Early use of meSPIM in observing melanoma cells is already offering new insights into the relationship between the cell behavior of cellular- and subcellular-scale mechanisms and the microenvironment in which these cells exist. The study notes, “The ability to image fine cellular details in controllable microenvironments revealedmorphodynamic features not commonly observed in the narrow range of mechanical environments usually studied in vitro.”

One such difference is the appearance of blebbing. Created by melanoma cells and lines, these small protrusions are thought to aid in cell mobility and survival. Using meSPIM, observers could follow the blebbing process in real-time. Formation of blebs on slides and within an extracellular matrix (ECM) showed significant differences in both formation and manipulation of the surrounding microenvironment.

The team is also using meSPIM to take a look at membrane-associated biosensorand cytosolic biosensor signals in 3D. They hope that investigation of proteins such as phosphatidylinositol 3-kinase (PI3K) and protein kinase C will help to further clarify the roles these signals play in reorientation of fibroblasts.

 

meSPIM combined with computer vision enables imaging, visualization, and quantification of how cells alter collagen fibers over large distances within an image volume measuring 100 mm on each side. (Photo Copyright: Welf and Driscoll et al.)   http://www.darkdaily.com/wp-content/uploads/meSPIM-500ppi-220×300.jpg

 

Seeing cancer cells in 3-D (w/ Video)

February 22, 2016

Extracted surfaces of two cancer cells. (Left) A lung cancer cell colored by actin intensity near the cell surface. Actin is a structural molecule that is integral to cell movement. (Right) A melanoma cell colored by PI3-kinase activity near the cell surface. PI3K is a signaling molecule that is key to many cell processes. Credit: Welf and Driscoll et al.  http://cdn.phys.org/newman/csz/news/800/2016/cancerin3d.png

Cancer cells don’t live on glass slides, yet the vast majority of images related to cancer biology come from the cells being photographed on flat, two-dimensional surfaces—images that are sometimes used to make conclusions about the behaviour of cells that normally reside in a more complex environment. But a new high-resolution microscope, presented February 22 in Developmental Cell, now makes it possible to visualize cancer cells in 3D and record how they are signaling to other parts of their environment, revealing previously unappreciated biology of how cancer cells survive and disperse within living things.

“There is clear evidence that the environment strongly affects cellular behavior—thus, the value of cell culture experiments on glass must at least be questioned,” says senior author Reto Fiolka, an optical scientist at the University of Texas Southwestern Medical Center. “Our microscope is one tool that may bring us a deeper understanding of the molecular mechanisms that drive cancer cell behavior, since it enables high-resolution imaging in more realistic tumor environments.”

In their study, Fiolka and colleagues, including co-senior author Gaudenz Danuser, and co-first authors Meghan Driscoll and Erik Welf, also of UT Southwestern, used their microscope to image different kinds of skin cancer cells from patients. They found that in a 3D environment (where cells normally reside), unlike a glass slide, multiple melanoma cell lines and primary melanoma cells (from patients with varied genetic mutations) form many small protrusions called blebs. One hypothesis is that this blebbing may help the cancer cells survive or move around and could thus play a role in skin cancer cell invasiveness or drug resistance in patients.

The researchers say that this is a first step toward understanding 3D biology in tumor microenvironments. And since these kinds of images may be too complicated to interpret by the naked eye alone, the next step will be to develop powerful computer platforms to extract and process the information.

“When we conceived of this project, we first asked what we wanted to measure and then designed a microscope and analytical platform to achieve this goal,” says co-first author Erik Welf, a cell biologist. “We hope that now instead of asking what we can measure, scientists will ask what we must measure in order to make meaningful contributions to cancer cell biology.”

The microscope control software and image analytical code are freely available to the scientific community.

More information: Developmental Cell, Welf and Driscoll et al.: “Quantitative Multiscale Cell Imaging in Controlled 3D Microenvironments” dx.doi.org/10.1016/j.devcel.2016.01.022

Read more at: http://phys.org/news/2016-02-cancer-cells-d-video.html#jCp

Quantitative Multiscale Cell Imaging in Controlled 3D Microenvironments

Erik S. Welf⁴, Meghan K. Driscoll⁴, Kevin M. Dean, Claudia Schäfer, Jun Chu, Michael W. Davidson, Michael Z. Lin, Gaudenz Danuser , Reto Fiolka

Dev Cell  22 Feb 2016;  Volume 36, Issue 4:462–475     DOI: http://dx.doi.org/10.1016/j.devcel.2016.01.022

Highlights

• •meSPIM allows microenvironmentally conscious 3D imaging/analysis of subcellular biology
• •Precisely controlled microenvironments reveal diverse morphological phenotypes
• •Isotropic resolution and high speed enable the quantification of 3D cell signaling and morphodynamics
• •Multiscale quantification of microenvironmental reorganization by cells

Summary

The microenvironment determines cell behavior, but the underlying molecular mechanisms are poorly understood because quantitative studies of cell signaling and behavior have been challenging due to insufficient spatial and/or temporal resolution and limitations on microenvironmental control. Here we introduce microenvironmental selective plane illumination microscopy (meSPIM) for imaging and quantification of intracellular signaling and submicrometer cellular structures as well as large-scale cell morphological and environmental features. We demonstrate the utility of this approach by showing that the mechanical properties of the microenvironment regulate the transition of melanoma cells from actin-driven protrusion to blebbing, and we present tools to quantify how cells manipulate individual collagen fibers. We leverage the nearly isotropic resolution of meSPIM to quantify the local concentration of actin and phosphatidylinositol 3-kinase signaling on the surfaces of cells deep within 3D collagen matrices and track the many small membrane protrusions that appear in these more physiologically relevant environments.

Read more: 3D Imaging of Cancer Cells Could Lead to Improved Ability of Pathologists and Radiologists to Plan Cancer Treatments and Monitor Cell Interactions | Dark Daily http://www.darkdaily.com/3d-imaging-of-cancer-cells-could-lead-to-improved-ability-of-pathologists-and-radiologists-to-plan-cancer-treatments-and-monitor-cell-interactions-301#ixzz45Enp2yT0

The research team believes this opens new possibilities for studying diseases at a subcellular level, saying, “Cell biology is necessarily restricted to studying what we can measure. Accordingly, while the last hundred years have yielded incredible insight into cellular processes, unfortunately most of these studies have involved cells plated onto flat, stiff surfaces that are drastically different from the in vivo microenvironment …

“Here, we introduce an imaging platform that enables detailed subcellular observations without compromising microenvironmental control and thus should open a window for addressing these fundamental questions of cell biology.”

Limitations of meSPIM

One significant issue associated with the use of meSPIM is the need to process the large quantity of data into useful information. Algorithms currently allow for automatic bleb detection. However, manual marking, while time consuming, still provides increased accuracy. Researchers believe the next step in improving the quality of meSPIM scans lie in computer platforms designed to extract and process the scan data.

Until this process is automated, user bias, sample mounting, and data handling will remain risks for introducing errors into the collected data. Yet, even in its early stages, meSPIM offers new options for assessing the state of cancer cells and may eventually provide pathologists and radiologists with additional information when creating treatment plans or assessments.

 

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

Bio-Inks and 3D BioPrinting

Posted in 3D Plotting Scaffolds, 3D Printing for Medical Application, BioInks, BioPrinting in Regenerative Medicine, tagged 3-D bioprinting, BioInk, bioprinting, hydrogel, RegenHu on April 4, 2016| Leave a Comment »

Bio-inks and 3D BioPrinting

Curator: Stephen J. Williams, Ph.D.

 

Bio-ink is a material made from living cells that behaves much like a liquid, allowing people to “print” it in order to create a desired shape. This material was developed by researchers at the University of Missouri, Columbia, with the goal of someday being able to do things like print replacements for failing organs. This technology is only in the very early stages of testing and development, but it shows promise.

To make bio-ink, scientists create a slurry of cells that can be loaded into a cartridge and inserted into a specially designed printer, along with another cartridge containing a gel known as bio-paper. After inputting the standards for the thing they want to print, the researchers trigger the printer, and the cartridges alternate layers to build a three dimensional structure, with the bio-paper creating a supportive matrix that the ink can thrive on.

Through a process that is not yet totally understood, the individual droplets fuse together, eventually latticing upwards through the bio-paper to create a solid structure. Understanding this process and the point at which cells differentiate to accomplish different tasks is an important part of creating a usable material; perhaps someday hospitals will be able to use it to generate tissue and organs for use by their patients.

 

The most obvious potential use for bio-ink is in skin grafting. With this technology, labs could quickly create sheets of skin for burn victims and other people who might be in need of grafts. By creating grafts derived from the patient’s own cells, it could reduce the risk of rejection and scarring. Bio-ink could also be used to make replacements for vascular material removed during surgeries, allowing people to receive new veins and arteries.

Eventually, entire organs could be constructed from this material. Since organs are in short supply around the world, bio-ink could potentially save untold numbers of lives, as patients would no longer have to wait on the transplant list for new organs. The use of such organs could also allay fears about contaminated organ supplies or unscrupulous organ acquisition methods.

 

RegenHu

Universal Matrix for 3D Tissue Printing

photo from http://www.regenhu.com/

BioInk^TM is a chemically-defined hydrogel to support growth of different cell types. It allows cell adhesion, mimics the natural extracellular matrix and is biodegradable.

BioInk^TM is provided as a ready-to-use chemically-defined hydrogel to print 3D tissue models. Exclusively designed for regenHU’s BioFactory® and 3DDiscovery® tissue and bio-printers.

A versatile, chemically-defined hydrogel, supporting cell attachment, growth, differentiation and migration. The BioInk^TM is suitable for long-term tissue cultivation (in vitro human dermis for up to 7 weeks).

 

 

 

 

 

 

 

A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation

• Matti Kesti^{a, 1},
• Michael Müller^{a, 1},
• Jana Becher^b,
• Matthias Schnabelrauch^b,
• Matteo D’Este^c,
• David Eglin^c,
• Marcy Zenobi-Wong^{a, ,}

• ^a Cartilage Engineering + Regeneration Laboratory, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland
• ^b Biomaterials Department, INNOVENT e.V. Jena, Prüssingstrasse 27 B, 07745 Jena, Germany
• ^c AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland

 

Layer-by-layer bioprinting is a logical choice for the fabrication of stratified tissues like articular cartilage. Printing of viable organ replacements, however, is dependent on bioinks with appropriate rheological and cytocompatible properties. In cartilage engineering, photocrosslinkable glycosaminoglycan-based hydrogels are chondrogenic, but alone have generally poor printing properties. By blending the thermoresponsive polymer poly(N-isopropylacrylamide) grafted hyaluronan (HA-pNIPAAM) with methacrylated hyaluronan (HAMA), high-resolution scaffolds with good viability were printed. HA-pNIPAAM provided fast gelation and immediate post-printing structural fidelity, while HAMA ensured long-term mechanical stability upon photocrosslinking. The bioink was evaluated for rheological properties, swelling behavior, printability and biocompatibility of encapsulated bovine chondrocytes. Elution of HA-pNIPAAM from the scaffold was necessary to obtain good viability. HA-pNIPAAM can therefore be used to support extrusion of a range of biopolymers which undergo tandem gelation, thereby facilitating the printing of cell-laden, stratified cartilage constructs with zonally varying composition and stiffness.

 

https://www.youtube.com/watch?v=9D749wZSlb0

For more information see:

http://www.slideshare.net/StephenJWilliamsPhD/clipboards/my-clips

 

And for more information on biopaper and methodology please see this pdf file courtesy of The First Symposium on BioPrinting in Tissue Engineering (see file) biopaper presentation

 

 

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

« Newer Posts - Older Posts »

• Follow Blog via Email

  Enter your email address to follow this blog and receive notifications of new posts by email.

  Email Address

  Follow

  Join 9,329 other subscribers

• Recent Posts

  • The Health Care Dossier on Clarivate PLC: How Cortellis Is Changing the Life Sciences Industry April 16, 2024
  • Live Notes from JP Morgan Healthcare Conference Virtual Endpoints Preview: January 8-9 2024 January 16, 2024
  • The Future of AI in Cardiology November 5, 2023
  • Overview of Alzheimer’s Disease and Novel Treatments Targeting Beta-Amyloid Deposits October 7, 2023
  • The Implications and Association of Stair Climbing with Atherosclerotic Cardiovascular Disease (ASCVD) October 6, 2023
  • The Nobel Prize in Physiology or Medicine 2023 October 2, 2023
  • The Current Impact and Future of Technology within Cardiovascular Surgery September 23, 2023
  • The Continued Impact and Possibilities of AI in Medical and Pharmaceutical Industry Practices September 18, 2023
  • Regulatory T cells (Tregs) are important for sperm tolerance and male fertility September 11, 2023
  • ChatGPT Chemistry Assistant for Text Mining and the Prediction of metal–organic framework (MOF) synthesis August 27, 2023

• Archives

  Archives Select Month April 2024  (1) January 2024  (1) November 2023  (1) October 2023  (3) September 2023  (3) August 2023  (2) July 2023  (2) June 2023  (7) May 2023  (4) April 2023  (2) March 2023  (5) February 2023  (2) January 2023  (3) December 2022  (2) October 2022  (6) September 2022  (2) August 2022  (1) July 2022  (3) June 2022  (3) May 2022  (8) April 2022  (10) March 2022  (7) February 2022  (7) January 2022  (3) December 2021  (3) November 2021  (4) October 2021  (11) September 2021  (5) August 2021  (8) July 2021  (21) June 2021  (8) May 2021  (10) April 2021  (8) March 2021  (15) February 2021  (17) January 2021  (20) December 2020  (10) November 2020  (12) October 2020  (26) September 2020  (17) August 2020  (22) July 2020  (27) June 2020  (33) May 2020  (26) April 2020  (42) March 2020  (22) February 2020  (11) January 2020  (7) December 2019  (20) November 2019  (13) October 2019  (11) September 2019  (3) August 2019  (8) July 2019  (25) June 2019  (47) May 2019  (40) April 2019  (27) March 2019  (29) February 2019  (17) January 2019  (50) December 2018  (14) November 2018  (17) October 2018  (18) September 2018  (17) August 2018  (8) July 2018  (20) June 2018  (22) May 2018  (17) April 2018  (12) March 2018  (20) February 2018  (26) January 2018  (16) December 2017  (6) November 2017  (20) October 2017  (13) September 2017  (16) August 2017  (16) July 2017  (19) June 2017  (20) May 2017  (32) April 2017  (21) March 2017  (10) February 2017  (24) January 2017  (21) December 2016  (43) November 2016  (8) October 2016  (40) September 2016  (67) August 2016  (59) July 2016  (75) June 2016  (37) May 2016  (95) April 2016  (152) March 2016  (175) February 2016  (196) January 2016  (139) December 2015  (90) November 2015  (287) October 2015  (237) September 2015  (115) August 2015  (96) July 2015  (63) June 2015  (44) May 2015  (53) April 2015  (76) March 2015  (95) February 2015  (83) January 2015  (75) December 2014  (75) November 2014  (88) October 2014  (135) September 2014  (117) August 2014  (88) July 2014  (88) June 2014  (109) May 2014  (60) April 2014  (85) March 2014  (58) February 2014  (72) January 2014  (107) December 2013  (104) November 2013  (136) October 2013  (62) September 2013  (32) August 2013  (46) July 2013  (74) June 2013  (110) May 2013  (112) April 2013  (86) March 2013  (92) February 2013  (63) January 2013  (63) December 2012  (46) November 2012  (71) October 2012  (84) September 2012  (82) August 2012  (122) July 2012  (59) June 2012  (34) May 2012  (46) April 2012  (2)

• Categories

  Categories Select Category 3D Printing for Medical Application  (234)    3D Plotting Scaffolds  (43)    BioInks  (33)       Biopolymer Blend Open Porous  (17)       Dental Applications  (10)    BioPrinting in Regenerative Medicine  (74)       Cell Level  (14)       MicroEngineering Cell-Tissue & Systems  (30)       Tissue Engineering  (35)    Cardiovascular and Vascular Systems  (29)       Artificial Vascular Structures  (9)       Cardiovascular Tissue  (8)    Drug Development using MultiOrgan Chip  (11)    Drug Development/Formulation using 3D Printing  (8)    MEMS  (16)       Bio-MEMS  (12)    Organ-on-a-Chip  (11)    Programmable Sensors (Carbon Nano Tubes)  (5) 3rd Party IP: Drug DIscovery  (1) 4D Printing and Meta Materials  (9) Academic Publishing  (222)    Key Opinion Leaders in eScientific Publishing – Interviews with  (8) Advanced Drug Manufacturing Technology  (93)    Antimalarial Preparation  (8)    Autologous Cell Therapy  (12)    Automated Cell Processing  (13) Allergy and Infectious Diseases  (12) Alzheimer’s Disease  (160)    Etiology  (77)    Medical Device Therapies for Altzheimer’s Disease  (14)    Pharmacotherapy and Cell Activity  (50) Anticancer Resistance  (28) Art Exhibits on the Human Condition  (1) Art Inspires Science  (3) Artificial Heart  (2) Artificial Intelligence – General  (194)    An executive’s guide to AI  (9)    Artificial Intelligence – Breakthroughs in Theories and Technologies  (94)    Artificial Intelligence Applications in Health Care  (95)       Artificial Intelligence in CANCER  (28)       Artificial Intelligence in Health Care – Tools & Innovations  (55)    Artificial Intelligence in Medicine – Application for Diagnosis  (52)       Artificial intelligence applications for cardiology  (23)          AI-assisted Cardiac MRI  (9)       Artificial Intelligence in Psychiatry  (5)       Deep Learning in Pathology  (14)    Artificial Intelligence in Medicine – Applications in Therapeutics  (50)    ChatGPT, GPT-4  (4)       ChatGPT at LPBI Group  (2)       ChatGPT in Academic Education  (3)    Machine Learning  (48)       Deep Learning  (8)       Natural Language Processing (NLP)  (25)    Machine learning in predicting type 2 diabetes  (2) Auditory and vision  (13) Autism Spectrum Disorders  (10) Autoimmune Inflammatory DIseases  (21)    Crohn’s disease  (5)    Tolerance-inducing Autoimmune Disease Therapeutics  (4)    Ulcerative Colitis  (3) Autophagosome  (3) Bacterial Resistance  (25) Behavior  (26) Behavioral Genetics  (21) Big Data  (79)    Intelligent Information Systems  (48) Bio Instrumentation in Experimental Life Sciences Research  (365)    Analytical Instruments Industry  (5)    Microfuidics  (8) Bio-Ethics  (14) BioBanking  (33) Biodegradable Drug-eluting Material  (7) Bioengineering & reverse engineering design  (42) BioIT: BioInformatics  (143) BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics  (126)    Advanced Computing Platform  (31)       Blockchain Transactions System  (6)          Platform for Content Monetization embedded Content Promotion  (1)    Pancreatic adenocarcinoma classifier  (4)    Simulation Modeling in NGS  (3) Biological Engineering  (41) Biological Networks  (190) Biological Networks, Gene Regulation and Evolution  (474)    Virology  (10) Biomarkers & Medical Diagnostics  (565)    VOC – Volatile Organic Compounds as BioMarkers  (2) Biomedical Measurement Science  (173) BioSimilars  (111) BioTechnology – Venture Creation  (126)    Foundations for supporting Science and Education  (12)    Philanthropy to Academic Institution  (2) BioTechnology – Venture Creation, Venture Capital  (105)    Seeking Talent  (3) BiVAD  (1) Blindness  (6) Bone Disease and Musculoskeletal Disease  (82) Brain Basis of Emotion  (5) Business Career Consideration  (1) Ca2+ triggered activation  (59) Calcium  (19) Calcium Signaling  (68) Calmodulin Kinase and Contraction  (35) Cancer – General  (177) Cancer and Current Therapeutics  (397)    interventional oncology  (42)       Breast Cancer – impalpable breast lesions  (17)       Prostate Cancer: Monitoring vs Treatment  (8) CANCER BIOLOGY & Innovations in Cancer Therapy  (1,092)    Anaerobic Glycolysis  (51)    Cachexia  (18)    Cancer Genomics  (69)       Circulating Tumor Cells (CTC)  (19)          Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood  (14)             mRNA  (5)          MagSifter chip  (1)       KRAS Mutation  (6)       Li-fraumeni syndrome.  (3)       TP53 – Germline mutations  (5)    cancer metabolism  (20)    Funding Opportunities for Cancer Research  (11)    Genomic Expression  (143)    Glioblastoma  (7)    Hexokinase  (14)    Loss of function gene  (18)    Metabolic Immuno-Oncology  (16)    Metastasis Process  (13)    Methylation  (32)    Microbiome and Responses to Cancer Therapy  (5)    Monoclonal Immunotherapy  (27)    mtDNA  (13)    Oxidative phosphorylation  (56)    Pancreatic cancer  (9)    Pyruvate Kinase  (27)    The NCI Formulary  (1)    tumor microenvironment  (13)    Warburg effect  (50) Cancer Informatics  (93) Cancer Prevention: Research & Programs  (125) Cancer Screening  (102) Cancer Vaccines: Targeting Cancer Genes for Immunotherapy  (25)    Engineering Enhanced Cancer Vaccines  (3) cancer-general  (1) Cardiac and Cardiovascular Surgical Procedures  (321)    Aortic Valve: TAVR, TAVI vs Open Heart Surgery  (87)       Prosthesis-Patient Mismatch (PPM) in TAVI vs SAVR  (2)       TAVI vs Open Heart Surgery  (6)       Transcatheter Aortic Valve Replacement via the Transcarotid Access  (2)       Transcaval TAVR Procedure  (3)       Valve-in-Valve Procedure  (4)    Atrial Fibrilation (a-Fib), Cardiac Pacing and Arrhythmias  (17)    BackBeat’s Cardiac Neuromodulation Therapy (CNT) bioelectronic therapy  (1)    CABG  (47)    Cancer Surgery of the Heart  (10)    Cardiovascular Fluid Management: algorithms  (1)    Heart Transplant  (15)    Heart-Lung Transplant  (10)    Implantation  (2)    Left Main Coronary Artery Disease (LMCAD)  (3)    Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart  (19)    Mitral Valve: Repair and Replacement  (63)       TMVR – Transcatheter Mitral Valve Repair  (4)    PCI  (104)       Bioresorbable Vascular Scaffold (BVS)  (3)       Invasive FFR for PCI  (2)       Multivessel PCI FFR Guidance  (1)       Robotic-assisted percutaneous coronary intervention  (1)       Stent Retriever in endovascular thrombectomy  (2)    Peripheral Arterial Disease & Peripheral Vascular Surgery  (63)       Abdominal Aorta  (20)       Carotid Artery  (15)       Limb ischemia  (4)       Thoracic Aorta  (16)    Pulmonary Valve Replacement and Repair  (3)    Renal Denervation  (20)    Replacement  (1)    Robotically assisted Cardiothoracic Surgery  (1)    Tricuspid Valve Repair  (7)    Vena Caval Filters: Device for Prevention of Pulmonary Embolism and Thrombosis  (1) Cardiovascular Pharmacogenomics  (169) Cargo  (3) Cell Biology  (320) Cell Biology, Signaling & Cell Circuits  (663)    Apoptosis  (17)    Autophagy-Modulating Proteins  (6)    “Antibody–enzyme conjugates”  (5)    Cell Processing System in Cell Therapy Process Development  (25)    Endoplasmic reticulum  (3)    Enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)  (3)    Ubiquitin  (10) Cerebrovascular and Neurodegenerative Diseases  (123)    Stroke  (9) Chemical Biology and its relations to Metabolic Disease  (461)    #BIGAxisSummit  (1)    Gut Microbiome and Obesity  (8) Chemical Genetics  (349) Child and Adolescent Psychiatry  (13) Childhood cancer  (15) Childhood malnutrition  (3) children  (2) Circulating Progenitor Cells  (27)    Bone marrow derived cells  (17)    Endothelial cells  (7)    Umbilical cord cells  (6) Clinical & Translational  (235) Clinical Diagnostics  (216)    Mass automation of plasma proteins  (13) Clinical Genomics  (136) Coagulation Therapy and Internal Bleeding  (83) Cognition  (46) Commercialization  (20) Components and IRB related issues  (4) Computational Biology/Systems and Bioinformatics  (465)    Computational Histopathology  (3)    Meta-analysis of transcriptome data  (9) Conference Coverage with Social Media  (477)    MassBio  (3) coronavirus  (18) COVID-19  (20) CRISPR/Cas9 & Gene Editing  (188)    CRISPR alternative for editing genes without cutting  (14)       CAST – Alternative to CRISPR/Cas9  (3)       Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration  (4)    CRISPR applied to Human Germ Line  (10)       Gene Editing Impact on Longevity  (4) CT  (19) Cytokines  (20) Cytoskeleton  (84) Developmental biology  (107) Diabetes Mellitus  (142)    Artificial Pancreas for Type 2 Diabetes  (1)    Artificial Pancreas for Type1 Diabetes  (5)    Gestational diabetes  (2) Diagnostic Immunology  (58) Diagnostics and Lab Tests  (127)    Liquid Biopsy: Circulating Tumor Cells in Urine and Blood  (8) Digital HealthCare – biotech & internet joint ventures  (46) Disease Biology  (333) Disease Biology, Small Molecules in Development of Therapeutic Drugs  (484) DNA repair  (72)    Apoptosis  (12)    Autophagy  (13)    Cell death pathways  (19)    Proteolysis  (8)    Proteosome  (8) Drug Delivery Platform Technology  (156)    Drug Carrier Design  (20)       Medication Remote Compliance Monitoring  (3)    Exosomes: Natural Carriers for siRNA Delivery  (9) Drug Toxicity  (74) Ecosystems & Industrial Concentration in the Medical Device Sector  (172)    Cardiac & Vascular Repair Tools Subsegment  (128)    Exec Compensation in the Cardiac & Vascular Repair Tools Subsegment  (14)    Massachusetts Niche Suppliers and National Leaders  (20) Electronic Health Record  (9) Embryology  (24) Empathy  (6) Endocrine Diseases  (60) Enzyme Induction  (46)    ion-transporting enzyme  (2)    K + -ATPase.  (1)    Na +  (2) Epigenetics and Environmental Factors  (32) Ethics and Leadership  (10) Executive Compensation – Big Pharma  (3) Fat soluble vitamins  (4) FDA  (68) FDA Regulatory Affairs  (355)    FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP, GLP, ISO 14155  (52)    ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics  (30) Fetal Ultrasound  (2) Fiction and medicine  (5) Frontiers in Cardiology and Cardiovascular Disorders  (920)    Acute Myocardial Infarction  (62)       Cardiogenic Shock  (5)    Anemia in CVD Patients  (6)    Cardio-Oncology  (4)    Cardiomyopathy  (57)    Cardiovascular Research  (187)       Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism  (64)       Pre-Clinical Animal Model Development  (23)    Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH)  (20)    Cost of Inpatient Stay for Cardiovascular Diagnosis for Admission  (1)    Electrophysiology  (108)       Ablation Procedure vs Drug Therapy  (2)       Arrhythmia Detection with Machine Learning Algorithms  (6)       Cardiotoxic Risks of Immune Checkpoint Inhibitors  (1)       Genomic Analysis of EKG Electrophysiology Genomics  (3)       implantable cardioverter defibrillator (ICD) and External Defibrillation  (1)       implantable pacemaker  (2)       Rare heart rhythm disorders and Long QT syndrome (LQTS)  (6)    Epigenetics and Cardiovascular Risks  (57)    Heart Failure (HF)  (48)       Acute coronary syndrome  (6)       congestive heart failure  (18)    Medical Devices R&D and Inventions  (208)       Assist Devices: LV  (3)       RV  (1)       Stents & Tools  (89)       Valves & Tools  (65)    Origins of Cardiovascular Disease  (419)       Atherogenic Processes & Pathology  (178)       Congenital Heart Disease  (34)          Genetic Mutations in Congenital Heart Disease  (4)       inflammation independent of lipid levels  (12)       Systemic Inflammatory Diseases as CVD Risk  (11)    Pharmacotherapy of Cardiovascular Disease  (353)       HTN  (173)       HTN in Youth  (8)       Resident-cell-based  (43)       Subarachnoid Hemorrhage (SAH)  (1)       Transthyretin amyloid cardiomyopathy (ATTR-CM)  (1)    Spontaneous Coronary Artery Dissection (SCAD)  (6)    Stroke  (14)       endovascular thrombectomy  (5)    Vascular Diseases  (21)       mesenteric ischemia  (3) Future Pandemics Inform-graphics  (1) Gastroenterology  (38) Gene Regulation  (228) Gene Regulation and Evolution  (135) Genetics & Innovations in Treatment  (172) Genetics & Pharmaceutical  (199) Genome Biology  (959)    Exosomes  (24)    Gene Therapy & Gene Editing Development  (38)    mRNA Therapeutics  (17)    Mutagenesis  (26)    Single Cell Genomics  (22)    Single-cell sequencing  (18)    Variation in human protein-coding regions  (32) Genomic Endocrinology  (42) Genomic Testing: Methodology for Diagnosis  (412) Genomics Pharmacy  (38) Global Market of Medical Devices Technology  (2) Global Medical Publishers by Country  (3) Global Partnering & Biotech Investment  (45) GLP  (4) Glycobiology: Biopharmaceutical Production  (15) Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics  (27) Health Care System by Country  (49)    AI Models in Healthcare  (8)    Centers for Medicare & Medicaid Services  (8)    Health in Israel  (2)    United States  (24)       Hospital-based Medical Innovations  (8)       Medical Recertification and Maintenance of Certification (MOC)  (1) Health Economics and Outcomes Research  (378)    Women Health  (15)       Heart and Brain Disease in Women  (3) Health Law & Patient Safety  (162)    and Bioethics  (13)    Biotechnology  (11)    Health Law Policy  (12) HealthCare IT  (136) Healthcare Reform  (112)    Accountable Care Organizations  (26)    Affordable Care Act  (29)       Repair  (1)       Repeal ACA  (1)       Replace  (1)    Federal Budget Appropriations  (26)    Healthcare costs and reimbursement  (55)    Indigent Nutrition  (14)    Medicare and Medicaid  (20)    Prescription Drugs Costs  (21)    Skilled Nursing Facilities  (6)    Technology Capital Expenses  (15)    Uninsured and Underinsured  (20) Hematology  (99)    Acute lymphocytic leukemia  (18)    Acute myelocytic leukemia  (21)    Hematopoiesis  (48)    Lymphoma  (21) History and physical exam  (6) Human aging  (27) Human Immune System in Health and in Disease  (237) Human Sensation and Cellular Transduction: Physiology and Therapeutics  (21) Image Processing/Computing  (41) Imaging-based Cancer Patient Management  (116) Immuno-Oncology & Genomics  (126)    mRNA platform in Drug DIscovery  (6) Immunodiagnostics  (128)    Cancer-Immune Interactions  (20)    CNS-Immune Interface  (3)    Neuronal Circuits  (4) Immunology  (114)    Adaptive Immune Response to Biomaterials and Tissue Repair  (10)    Antibody Responses Predict Antigen Exposure  (15)    Cytokine Receptor Structure  (8)    Human Antibody Response  (17)    Human Circulating Antibody Repertoire  (10)    Human Naive B Cell Repertoire  (8)    MHC Repertoires for Antigen Prediction  (8)    Protection Against Autoimmune Disease  (9)    Synthetic Immunology: Hacking Immune Cells  (12) Immunotherapy  (121)    CAR-T  (13)    combination immunotherapies.  (11)    Efficacy of Anti-Tumor T Cells  (11)    Engineering Better T Cells  (7)    Immune Engineering  (13)    Immune Modulatory  (13)    Integrin-targeted Combination Immunotherapy  (5)    Modulating Macrophages in Cancer Immunotherapy  (11)    NK Cell-Based Cancer Immunotherapy  (16)    Synergistic Innate and Adaptive Immunotherapy  (13) Income Disparity  (2) Infectious Disease & New Antibiotic Targets  (162)    Antibiotic resistance  (7)    Viral diseases  (37)       Myocarditis  (1) Infectious Disease Immunodiagnostics  (56)    Virology – Vector-borne DIsease  (17) Inflammasome  (26)    Anti-tumor necrosis factor drugs (TNF inhibitors)  (2) Innovation in Immunology Diagnostics  (107)    Universal Immune Cell Therapies (uICT)  (10) Innovations  (185)    R&D Expenditure  (8) Innovations in Neurophysiology & Neuropsychology  (142)    Age and Life Expectancy  (1)    autism spectrum disorder  (1)    Circadian Rhythm and Sleep  (6)    hNPCs  (1)    Nervous System Function  (2)    Relapsing Multiple Sclerosis  (1) Intellectual Property  (76)    Disputes and Settlements  (9)    IP Valuation Models – Pricing Intangible Assets  (5)    Patent Law in Biotech  (12) Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough  (108) International Global Work in Pharmaceutical  (188) Interventional Oncology: Radiofrequency Ablation, Transarterial Chemoembolization, Microwave Ablation and Irreversible Electroporation (IRE)  (12) Interviews with Scientific Leaders  (302)    Albany Medical Center Prize in Medicine and Biomedical Research  (1)    Annual Breakthrough Prize  (2)    Annual Lewis S. Rosenstiel Award  (1)    Awards in Cardiology and Cardiovascular Medicine  (4)    CEOs of Biotech Companies  (2)    Gerald D Aurbach Award for Outstanding Translational Research  (1)    Interviews with Key Opinion Leaders (KOLs)  (7)    James Prize in Science and Technology Integration  (1)    Jessie Stevenson Kovalenko Medal – Medical Sciences  (1)    Lemelson-MIT Prize  (1)    Life Sciences Breakthrough Prize  (3)    Mosteller Statistician of the Year Award  (1)    Mourning the Loss of a Scientific Leader  (2)    National Academy of Sciences AWARDS  (2)    Nobel Prize Winners  (21)    Noble Prize (Not Nobel Prize)  (1)    Paul Marks Prize for Cancer Research  (1)    Russ Prize recognizes bioengineering achievements worldwide  (1)    The Dan David Prize  (5)    Warren Alpert Foundation Prize Recipients  (3)    Wolf Prize  (1)    Wolf Prize in Medicine  (1)    women in science  (3) Investment in Technological Breakthrough  (60) Ionic Transporters Na+  (25) IP Development by LPBI Group Team  (10) IP Development by LPBI Group Team & Other Organizations  (7) ISO 14155  (3) Joint Venture – SBH & M3DP: SOP and Arrangements  (1) Justice & Law  (1) K  (15) Lab-on-a-chip  (2) Landscape  (1) Lasers and photonics  (18)    Midrange IR spectroscopy  (1) Law and Medicine Conflicts  (14) Leadership, Power, Social Interlocking Connections  (13) Lipid metabolism  (109)    Fatty acids  (38)    Lipids  (38)    PCSK9 Inhibitor Therapy  (19) Lipidomics  (11) Liposome  (4) Liver & Digestive Diseases Research  (120) LPBI Group, e-Scientific Media, DFP, R&D-M3DP, R&D-Drug Discovery, US Patents: SOPs and Team Management  (129)    Award Nominations  (5)    BioMed e-Books e-Series by LPBI Group  (8)    Feedback from Investors: LPBI Portfolio of Five Businesses  (2)    LPBI Group Founder – Aviva Lev-Ari  (22)    PhD  (1)    RN  (1) LPBI Management  (15) Massachusetts Academy of Sciences (MAS)    (2) Materials Science & Engineering  (37)    Organic BioElectronics  (2) Math  (13)    Great Discoveries  (7) Mechanical Assist Devices: LVAD  (4) Medical and Population Genetics  (191) Medical Devices R&D Investment  (239)    21st Century Cures Act  (2)    CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP  (13)    Rhythm management device hardware: dual-chamber pacemakers  (1)       Systolic HTN  (1) Medical Imaging Technology  (55) Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound  (160)    Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI)  (3)    Echocardiography  (2)    MRI  (17)    Noninvasive Diagnostic Fractional Flow Reserve (FFR) CT  (5)    Ultra Sound  (7) Melatonin & Circadian Regulation  (9) memory loss  (1) Metabolism  (236)    Biochemical pathways  (142)       Enzymes and isoenzymes  (72)          Dehydrogenase  (16)          Kinase  (28)          Phosphatase  (9)          Phosphorylase  (22)          tyrosine decarboxylases  (3)    Inosine nucleotides  (9)    Leloir pathway  (6)    microbiome  (7)    Pentose monophosphate shunt  (14)    Pyridine nucleotides  (28)       Pyridine nucleotide transhydrogenase  (7) Metabolomics  (318) Methods  (37) Mg++  (10) Microbiologial genetics  (34) Microbiology  (67)    Virology  (14) Micronutrients  (16) Microvesicle  (7) Microwave Ablation and Irreversible Electroporation (IRE)  (1) Mobile Healthcare  (4) Molecular Genetics & Pharmaceutical  (375)    Organoids  (3) Monoclonal antibody therapy  (13) Mutant Gene Expression  (42) Myocardial adenine nucleotide metabolism  (6) Myocardial Ischemia  (26) Myocardial Metabolism  (36) Na-K transport  (40) Na-K-ATPase  (27) Nanotechnology for Drug Delivery  (97) Nephrology  (46) Nephrology & Regenerative medicine  (9) Neurodegenerative Diseases  (88)    hNPCs  (3)    MS  (5) Neurohumoral Transmission  (67)    Ca2+ triggered activation  (20)    Calmodulin  (13)    Parkinson’s disease dyskinesia levodopa  (3)    PKC  (13)    Synaptic vesicle  (20) Neurological Diseases  (121) Neuroscience  (126) Next Generation Sequencing (NGS)  (25)    Nanopore sequencing  (1) NIH Common Fund  (1) Nitric Oxide in Health and Disease  (136) Nuclear Medicine  (11) Nutrigenomics  (68) Nutrition  (194)    Nutritional Supplements: Atherogenesis, lipid metabolism  (49) Nutrition and Phytochemistry  (61)    Minerals in Medicine  (4)    Plant extract  (22) Nutrition Disorders  (30) Nutritional Supplements: Atherogenesis  (31) Obesity  (18) Oligonucleotide Therapeutics & Delivery  (7) Oncolytic virus & OncoViro-Therapy  (21)    Synthetic Virology  (1) Organ-on-a-Chip & 3D Printing in Life Sciences  (7) Pain: Etiology, Genetics & Innovations in Treatment  (24) Parasitology  (5)    Malaria  (4)    Tropical diseases  (1) Patents  (34) Patient Experience  (64)    Art therapy  (1)    Hospital reputation  (7)    Humor  (1)    Music therapy  (2)    Pain Alleviation  (7)    Patient Outlook  (28)    Reputation of Interventionist  (4)    Support Staff  (13)    Supportive therapies  (6)       laughfter  (1)    Surgical Procedure  (7) Patient Experience: Personal Memories of Invasive Medical Intervantion  (30) Patient’s Voice: Personal Experience with Invasive Medical Procedures  (18) Perioperative Statins at Noncardiac Surgery  (2) Personal Health Applications: Tech Innovations serves HealhCare  (36) Personalized and Precision Medicine & Genomic Research  (717)    Longevity  (2)    New Drug Approval  (5)    Patient-centered Medicine  (35)       cell-based therapy  (8)       stem cell biology and patient-specific  (6)    Personalized Medicine Coalition  (8)    Precision Cancer Medicine  (18) Phagophore  (2) Pharmaceutical Analytics  (259)    Pharmacologic toxicities  (61) Pharmaceutical Discovery  (107)    Rapid automation of plasma protein pools  (16) Pharmaceutical Drug Discovery  (198)    Drug Development Process  (55)       Drug Discovery Chemistry  (29)    drug repurposing  (10) Pharmaceutical Industry Competitive Intelligence  (339)    Pharmacovigilance  (6)    Value-based Drug Pricing  (8) Pharmaceutical R&D Informatics  (43) Pharmaceutical R&D Investment  (297) Pharmacodynamics and Pharmacokinetics  (24) Pharmacogenomics  (157) Photography Collection  (1) Physics  (12) Placenta  (7) Population genetics  (25) Population Health Management  (192)    Evolution of Biology Through Culture  (14)    U.S. Employment-to-Population Ratio  (8) Population Health Management, Genetics & Pharmaceutical  (623)    COVID-19  (155)       Biomarkers: Inflammation  (36)       Cancer Researchers Fighting COVID-19  (14)       COVID-19 effects on Human Heart  (15)       COVID-19: Pandemic Surgery Guidance  (19)       Economic Impact of Coronavirus Pandemic  (41)       number of asymptomatic infections  (27)       Treatment Protocols for COVID-19  (62)    SARS-CoV-2  (138)       Coronavirus Gene Expression  (65)          SARS-CoV-2 circulating variants   (14)          SARS-CoV-2 Viral Variants  (18)       Glycosylation and its Role in SARS-CoV-2 Viral Pathogenesis  (2)       Immune-Mediation (independent immunopathology: lung and reticuloendothelial system)  (29)       Mechanisms of infection by SARS-CoV-2  (21)       SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus  (35)          SARS-COV2 Hijacking the Complement and Coagulation Systems  (19)       Seasonality & Environmental Factors in Resurgence  (26)       Serology tests for coronavirus antibodies  (44)       T-cell response to SARS-CoV-2 infection  (14)       Vaccinology  (51)          Mechanism of Thrombosis with AZ & J&J COVID-19 Vaccines  (5)       Virtual Drug Molecule Screening targeting SAR-CoV-2 proteins  (8)    Virus Infective Acute Respiratory Syndrome: SARS-CoV  (92) Population Health Management, Nutrition and Phytochemistry  (151) Preimplantation Genetic Diagnosis and Reproductive Genomics  (13) Protein-energy malnutrition  (12) Proteomics  (360)    Amino acids  (52)    Proteins  (134) Pulmonary diseases  (16)    Lung and pulmonology  (15) Pulmonary pathology  (8) Radio Frequency (RF)-based Surgical Solutions  (2) REAL TIME Conference Coverage Twitter’s Hashtags and Handles per Presentation/session  (31) Regenerative Biology and Medicine  (92) Regulated Clinical Trials: Design, Methods, Components and IRB related issues  (265) Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics  (113) Reproductive Biology & Bio Instrumentation  (78) RNA Biology  (81)    RNA interference (RNAi) therapeutic  (4) RNA Biology, Cancer and Therapeutics  (62) RVAD  (1) SBIR, SBA, NIH, NSF  (3) Schizophrenia  (16) Scientific & Biotech Conferences: Press Coverage  (174) Scientific Publishing  (607)    Curation  (584)       Curation methodology  (40)       De novo synthesis  (16)       Dialectic  (17)       Discovery process  (71)       Evolutionary cognition  (52)       Experimental validation  (90)       Explanatory  (91)       Historical relevance  (71)       Technology Advance Assessment of  (69)       Theoretic convergence  (27)    Open Access Journals  (37) Scientist: Career considerations  (196)    Big Data & Analytics  (17)    Data Science  (13)    Women in Life Sciences  (11) Scoop.it  (19) Sensors & Analytics  (18) Sepsis  (2) Severe Autism  (3) Signaling  (100)    Phosphorylation  (42)    S-nitrosylation  (13)    Ubiquitinylation  (33) Signaling & Cell Circuits  (129) single cell sequencing  (2) Small Molecules in Development of Therapeutic Drugs  (70) Social Development  (15) Specialized 3D BioPrinters (Cornea  (1) Statistical Methods for Research Evaluation  (137) Stem Cells for Regenerative Medicine  (175)    Cardiac muscle regeneration  (19)    Competition in regenerative stem cell science  (17)    Human neural progenitor cells  (7)    Skeletal muscle regeneration  (9) STORM  (2) Stress Disorders  (19) Substance Abuse  (4) Systemic Inflammatory Response Related Disorders  (160)    Inflammatory Pathophysiology  (8) Technology Transfer: Biotech and Pharmaceutical  (353) therapeutics  (3) Tissue Engineering and Regenerative Medicine  (22) Tissue Microenvironment  (4) Transarterial Chemoembolization  (2) Transcriptomics  (43) Transformative Technologies in Healthcare  (14) Translational Science  (226)    Best evidence  (52)    Bias measurement tools  (2)    Evidence-based decision-making  (27)    Inferential analysis  (25)    Intra-rater error  (1)    Quality Assurance  (8)    Random Error  (2)    Systematic Error (Bias)  (6)    Total error  (2)    Translational Effectiveness  (49)    Translational Research  (89) Trends in Global Economy  (6) Uncategorized  (1,009) Unfolded Protein Response (UPR)  (6) US and Global Economy: Trends and Findings  (9) Venture Capital  (45)    Income Geographic Distribution  (2)    Institutional Capital Raised by Female Founders  (6) virology  (9) Vision  (7) Voices of Patients and Healthcare Providers  (21) Water Transporters  (8) Wearable Tech + Digital Health  (4) Anemia  (21) Neutropenia  (8) Neutrophilia  (9) Platelet count disorder  (9) Folate and B12  (7) Iron deficiency  (5) Myelodysplasia  (12) Myelofibrosis  (10)

• Meta

  • Log in
  • Entries feed
  • Comments feed
  • WordPress.org

• • 2012pharmaceutical
  • Amandeep Kaur
  • Aashir Awan, Phd
  • Abhisar Anand
  • Adina Hazan
  • Alan F. Kaul, PharmD., MS, MBA, FCCP
  • alexcrystal6
  • anamikasarkar
  • apreconasia
  • aptubman
  • Arav Gandhi
  • aviralvatsa
  • David Orchard-Webb, PhD
  • danutdaagmailcom
  • Demet Sag, Ph.D., CRA, GCP
  • Dror Nir
  • dsmolyar
  • Ethan Coomber
  • evelinacohn
  • Gail S Thornton
  • Irina Robu
  • jayzmit48
  • jdpmd
  • jshertok
  • kellyperlman
  • Ed Kislauskis
  • larryhbern
  • Madison Davis
  • marzankhan
  • megbaker58
  • ofermar2020
  • Dr. Pati
  • pkandala
  • ritusaxena
  • Rick Mandahl
  • sjwilliamspa
  • Srinivas Sriram
  • stuartlpbi
  • Dr. Sudipta Saha
  • tildabarliya
  • zraviv06
  • zs22